The principal hypothesis of this Proposal is that ventilatory insufficiency and respiratory failure will inevitably occur even in resting man during CO2-free breathing at ambient gas densities, and at pressures not much greater than those to which men have already been exposed in pressure chamber simulation of deep diving. The experiment aim is to define conditions leading to failure in the goat, so they can be predicted and avoided by man. In prior work at this Institute, gas density at 22 grams/liter has been found to decrease respiratory CO2 reactivity in man by a factor of 6 compared to reactivity at 1 ATA, due to mechanical effects of "loading". Oxygen at 3 ATA reduced CO2 reactivity (also in man) by a factor of 2, presumably due to decrease in chemoreceptor activity. Since hyperoxia is used during decompression from exposure to pressure, and in therapy of decompression sickness at any pressure, it is proposed to investigate not only effects of extremely high gas density in normoxia, but to study conditions of hyperoxia together with high gas density which induce ventilatory insufficiency and failure in the goat. Results obtained in unanesthetized goats will be applied to prediction in man by matching effects of graded increase in gas density and of hyperoxia on CO2 reactivity obtained in goats to data already systematically obtained in man at this Institute for gas densities from 0.8 to 22 grams/liter and for oxygen at 0.2, 1.0, 2.0 and 3.0 atm. Initial exposures will be with non-invasive measurements. Once conditions of ventilatory insufficiency have been defined, invasive measurements will be added to better define physiological events associated with respiratory decompensation and failure. The investigations will be in three Phases, and will use CF4, Ne, and crude Ne (75% Ne, 25% He) with oxygen in appropriate mixtures at the range of pressures from 1 to 50 ATA to provide dose-response data on CO2 reactivity at 0.2, 1.0 and 2.0 atm of oxygen over the range of gas densities to and including failure of ventilatory control.